Background: Ertapenem, a group I carbapenem antibiotic, has been shown to be safe and effective in treating adults with complicated intra-abdominal (cIAI) or acute pelvic infection (API). This study evaluated ertapenem for treating these infections in children.Methods: In an open-label study, children aged 2 to 17 years with cIAI or API were randomized 3:1 to receive ertapenem or ficarcillin/clavulanate. Children 13 to 17 years of age received 1 g parenterally daily, and those 2 to 12 years of age received 15 mg/kg twice daily. Patients < 60 kg received ticarcillin/ clavulanate 50 mg/kg 4 to 6 times daily and 3.1 g 4 to 6 times daily for those >= 60 kg. Patients were assessed for safety and tolerability throughout the study and for efficacy after the completion of therapy.Results: One hundred five patients, 72 (69%) with clAl, received >= 1 dose of study drug and were included in the safety analysis. Eighty-one patients were treated with ertapenem. Infusion site pain was the most common drug-related adverse event in both groups. In the modified intent-to-treat analysis, the age-adjusted posttreatment clinical response rates were 87% (43/50 patients) and 100% (25/25 patients) in the clAl and API patients, respectively, for ertapenem and 73% (11115 evaluable patients) and 100% (8/8 evaluable patients), respectively, for ticarcillin/clavulanate. Overall age-adjusted response rates were 91% (68/75 evaluable patients) for ertapenem and 83% (19/23 evaluable patients) for the comparator.Conclusions: This study suggests that ertapenem is generally safe and efficacious for treating clAl or API in pediatric patients. (c) 2007 Published by Excerpta Medica Inc.

Background Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI. Methods A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14–35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations. Results A total of 825 patients received ≥ 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [ P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [ P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [ P = 0.435]) were the most frequently reported adverse events. Conclusion This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.

Hepatic abscess—amebic or pyogenic—can be diagnosed with great accuracy by either ultrasonography or computed tomographic (CT) scanning. Ultrasound is the modality of choice and will detect almost 100% of abscesses. Confirmation of a diagnosis of amebic liver abscess is made by the indirect hemagglutination test that should be positive in almost 100% of cases. Cultures of pus from the abscess and from the blood must be obtained in cases of pyogenic liver abscess. A positive culture of pus from the abscess has been achieved in 90% of cases. Ultrasound or CT guidance is utilized in aspiration of a hepatic abscess.

When a transmetatarsal amputation (TMA) is required, successful long-term limb salvage is questioned. We evaluated the influence of TMA on limb salvage in patients undergoing lower extremity revascularization. Patients who had distal bypasses extending to the infrapopliteal arterial tree and adjunctive TMA were retrospectively reviewed. Limb salvage was determined with life-table analysis. Twenty-four patients (29 limbs) were evaluated: 15 male and 9 female. Average age was 64.2 years old. Gangrene was the indication for bypass and TMA in 25 (86.2%) patients. Seven limbs were lost to follow-up. Nine of the remaining 22 limbs required below-knee (8) or above-knee (1) amputations, seven limbs within the first 3 months. In the group of patients who had major amputations within the first 3 months, graft thrombosis was the cause of leg amputation in six (85.7%) cases. No significant predictors of early major amputation were identified. Limb salvage was 62 per cent at 1 year in the TMA group. In comparison, among historical controls requiring distal revascularization and no adjunctive toe or foot amputations, limb salvage was 76.5 per cent (P = NS). Long-term limb salvage is dependent on successful lower extremity revascularization. Requirement for TMA should not influence the decision for limb salvage.

Purpose: This study was undertaken to define the long-term effects of renal revascularization on blood pressure, and renal and cardiac function in patients with Takayasu arteritis-induced renal artery stenosis (TARAS).Methods: Twenty-seven patients (25 women; mean age, 27 years) with TARAS underwent intervention. Primary, primary assisted, and secondary patency rates were determined, and the late effects on blood pressure, renal and cardiac function, and survival were analyzed.Results: All patients had hypertension (mean blood pressure, 167/99 mm Hg; 2.5 antihypertensive medications per patient). Mean estimated glomerular filtration rate in patients riot receiving hemodialysis was 76 mL/min, and in five patients serum creatinine concentration was greater than 1.5 mg/dL. Three patients were hemodialysis-dependent, and two had intractable congestive heart failure. Forty interventions were performed, including 32 aortorenal bypass procedures, two repeat implantations, four nephrectomies, and two transluminal angioplasty procedures. Postoperative morbidity was 19%. There were no deaths. During follow-tip (mean, 68 months), three graft stenoses, all due to intimal hyperplasia, and three graft occlusions occurred. Two of three graft stenoses were successfully revised. At 1, 3, and 5 years of follow-up, primary patency was 87%, 79%, and 79%, respectively; primary assisted patency was 93%, 89%, 89%, respectively; and secondary patency was 93%, 89%, and 89%, respectively. Intervention resulted in a decrease in blood pressure to a mean of 132/79 mm Hg (P < .0001), and the need for antihypertensive medications was reduced to one per patient (P < .01). Mean glomerular filtration rate increased to 88 mL/rnin (P < .005), and two patients no longer required hemodialysis. Congestive heart failure resolved in both patients, and did not recur. There were three deaths during follow-up, with 5-year and 10-year actuarial survival of 96% and 80%, respectively.Conclusions. Renal revascularization to treat TARAS is durable, has a salutary effect on blood pressure, and enhances long-term renal and cardiac function. This response establishes renal revascularization as a successful and durable intervention for TARAS, and a benchmark to which other therapies should be compared.

Objective. To examine the clinical efficacy and safety of ertapenem, a novel beta-lactam agent with wide activity against common pathogens encountered in intraabdominal infection.Summary Background Data Ertapenem has a pharmacokinetic profile and antimicrobial spectrum that support the potential for use as a once-a-day agent for the treatment of common mixed aerobic and anaerobic infections.Methods. This prospective, randomized, controlled, and double-blind trial was conducted to compare the safety and efficacy of ertapenem with piperacillin/tazobactam as therapy following adequate surgical management of complicated intraabdominal infections.Results. Six hundred thirty-three patients were included in the modified intent-to-treat population, with 396 meeting all criteria for the evaluable population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was most common (approximately 60% in microbiologically evaluable population). A prospective, expert panel review was conducted to assess the adequacy of surgical source control in patients who were failures as a component of evaluability. For the modified intent-to-treat groups, 245 of 311 patients treated with ertapenem (79.3%) were cured, as were 232 of 304 (76.2) treated with piperacillin/tazobactam. One hundred seventy-six of 203 microbiologically evaluable patients treated with ertapenem (86.7%) were cured, as were 157 of the 193 (81.2%) treated with piperacillin/tazobactam.Conclusions. In this study, the efficacy of ertapenem 1 g once a day was equivalent to piperacillin/tazobactam 3.375 g every 6 hours in the treatment of a range of intraabdominal infections. Ertapenem was generally well tolerated and had a similar safety and tolerability profile to piperacillin/tazobactam. A formal process for review of adequacy of source control was found to be of benefit. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of intraabdominal infections.

The efficacy and safety of intravenous (IV) ertapenem, 1 and 1.5 g once a day, for treatment of adults with complicated intra-abdominal infection were compared with those of IV ceftriaxone 2 g once a day plus IV metronidazole 500 mg every 8 h. After at least 3 days of IV therapy and satisfactory clinical response, patients could be switched to oral ciprofloxacin plus metronidazole. Fifty-nine patients were randomized to receive ertapenem 1 g and 51 to receive ertapenem 1.5 g; 55 patients were randomized to each comparator group. At the test of cure, 4–6 weeks post therapy, in the 1 g cohort, 84% (26/31) of patients treated with ertapenem and 85% (35/41) with comparator therapy had a favourable clinical and microbiological assessment. Success rates in the 1.5 g cohort were 83% (22/29) and 77% (24/31) in the ertapenem and comparator groups, respectively. Drug-related adverse events were generally similar in both treatment groups. Ertapenem 1 or 1.5 g once a day followed by optional oral therapy appeared similar to combined therapy with ceftriaxone plus metronidazole with the same optional oral switch for treatment of complicated intra-abdominal infections in adults. Although not compared directly in a randomized fashion, the efficacy and safety profiles of ertapenem 1 and 1.5 g appeared comparable. Ertapenem was generally well tolerated and had an overall safety profile similar to ceftriaxone plus metronidazole.

PURPOSE:The purpose of this study was to review the natural history and clinical outcome of patients with infrainguinal autogenous graft infection (IAGI), to evaluate the effectiveness of attempted graft preservation, to determine those variables associated with graft salvage, and to better determine optimal treatment. STUDY DESIGN:We retrospectively reviewed the records of patients undergoing infrageniculate vein grafts at three hospitals between 1994 and 2000 who had a wound infection involving the graft. Clinical and bacteriologic variables were analyzed and correlated with graft salvage, limb salvage, and clinical outcome. RESULTS:During this 7-year period, 487 patients underwent an infrageniculate vein graft, and 68 (13%) had clinical evidence of IAGI. Twenty-seven patients presented with drainage from the wound, 15 with wound separation and cellulitis, 18 with soft tissue infection extending to the graft, 4 with an abscess and cellulitis, and 4 with bleeding. Ten patients (15%) had systemic symptoms (defined as a white blood cell count > 15,000 and temperature > 38.5 degrees C). Forty infections developed in the thigh, 17 in the groin, and 11 in the lower leg. An anastomosis was exposed in 15 patients. Wound cultures were positive for bacteria in 52 patients, and most infections were due to Staphylococcus aureus (18 patients) and S epidermidis (12 patients). Pseudomonas was cultured from seven infections. Twelve patients had polymicrobial infections. The interval from operation to infection ranged from 7 to 180 days. All patients were treated with oral antibiotics, 48 after intravenous antibiotics. Forty-five patients had operative debridement, including 18 who had muscle flap coverage. Four patients presented with hemorrhage, and three had immediate graft ligation and one graft excision. Follow-up ranged from 5 to 68 months (mean, 24.3 months), with 61 patients currently alive. Two patients died as a result of the IAGI (mortality rate, 2.9%). One had undergone a below-knee amputation, and one had a nonhealed wound but intact limb. Overall, 61 wounds (91%) healed, 4 patients required below-knee amputations, and 3 wounds did not heal. Fifty-eight grafts remained patent, 6 thrombosed, and 4 were ligated to control hemorrhage. Of the 61 wounds that healed, the time required for healing ranged from 7 to 63 days. No patient with bleeding died because of the acute episode. No patient had delayed hemorrhage. All 18 patients treated with a muscle flap healed. Bleeding (P <.001), elevated white blood cell count (P <.029), fever (P <.001), and renal insufficiency (creatinine level > 1.5; P <.056) were the only variables statistically significant in predicting graft failure or limb loss. With the use of life-table analysis, graft patency was 94%, 72%, and 72% at 1, 3, and 5 years, and limb salvage was 97%, 92%, and 92% at the same intervals, respectively. CONCLUSIONS:Most patients with an IAGI can be successfully treated with graft and limb preservation. In contrast to earlier studies, an exposed anastomosis, interval to infection, or Pseudomonas infection is not associated with graft failure. Graft salvage is less likely in patinets with fever, leukocytosis, and renal insufficency, but because most grafts remained patent, graft preservation is recommended for these patients. Graft ligation or excision should be reserved for patients presenting with bleeding or sepsis.

Purpose: The purpose of this study was to determine the effectiveness of treatment of patients with combined arterial and venous insufficiency (CAVI), evaluate variables associated with successful ulcer healing, and better define criteria for interventional therapy.Study design: We retrospectively reviewed the records of patients treated at four institutions from 1995 to 2000 with lower extremity ulcers and CAVI. Arterial disease was defined as an ankle/brachial index less than 0.9, absent pedal pulse, and at least one in-line arterial stenosis > 50% by arteriography. Venous insufficiency was defined as characteristic clinical findings and duplex findings of either reflux or thrombus in the deep or superficial system. Clinical, demographic, and hemodynamic parameters were statistically analyzed with multiple regression analysis and correlated with ulcer healing and limb salvage.Results: Fifty-nine patients with CAVI were treated for nonhealing ulcers that had been present from 1 to 39 months (mean, 6.4 months). All patients had edema. The mean ankle/brachial index was 0.55 (range, 0-0.86). Treatment included elastic compression and leg elevation in all patients and greater saphenous vein stripping in patients with superficial venous reflux. Fifty-two patients underwent arterial bypass grafting, three underwent an endarterectomy, one underwent superficial femoral artery percutaneous transluminal angioplasty, and three underwent primary below-knee amputation. For purposes of analysis, patients were divided into four groups according to the pattern of arterial and venous disease and the success of arterial reconstruction. Group 1 consisted of 22 patients with a patent arterial graft, superficial venous incompetence, and normal deep veins. Group 2 consisted of seven patients with a patent graft, superficial reflux, and deep venous reflux. Group 3 included 22 patients with a patent graft and deep venous thrombosis (DVT), and group 4 included eight patients with an occluded arterial graft. Follow-up ranged from 2 to 47 months (mean, 21.6 months). Forty-nine patients remained alive, and 10 died of unrelated causes. During follow-up, 48 of the 56 treated arteries remained patent and eight occluded. Thirty-four ulcers (58%) healed, 18 ulcers (31%) did not heal, and 7 patients (12%) required below-knee amputation for nonhealed ulcers and uncontrolled infection. No patient with graft occlusion was healed, and 12 ulcers persisted despite successful arterial reconstruction. Twenty-one (78%) of 27 patients undergoing greater saphenous vein stripping were healed, but none of these patients had DVT. The mean interval from bypass graft to healing was 7.9 months. Thirty-two (68%) of 46 patients without prior DVT were healed, whereas only two (15%) of 13 patients with prior DVT were healed, and this variable, in addition to graft patency, was the only factor statistically significant in predicting healing (P < .05).Conclusions: Ulcers may develop anywhere on the calf or foot in patients with CAVI, and healing requires correction of arterial insufficiency. Patients with prior DVT are unlikely to heal, even with a patent bypass graft. Ulcer healing is a lengthy process and requires aggressive treatment of edema and infection, and successful arterial reconstruction. Patients with a prior DVT are unlikely to benefit from aggressive arterial or venous reconstruction.

BACKGROUND:Alatrofloxacin, the prodrug of trovafloxacin, is a novel fluoroquinolone antimicrobial agent with a broad spectrum, including activity against gram-positive and gram-negative aerobes and anaerobes. Its pharmacokinetic properties (long half-life, excellent tissue distribution, and good safety profile) suggest a role in surgical prophylaxis. This prospective, multicenter, double-blind trial compared alatrofloxacin with cefotetan, an approved drug for surgical prophylaxis, in reducing postoperative infections.METHODS:The efficacy and safety of a single 200-mg intravenous dose of alatrofloxacin were compared to a single 2-g intravenous dose of cefotetan in 492 patients undergoing elective colorectal surgery. The efficacy of alatrofloxacin as a prophylaxis for wound, intra-abdominal, or remote-site postoperative infectious complications was compared with cefotetan in 317 clinically evaluable patients; 161 received alatrofloxacin and 156 received cefotetan. The patients were monitored for infections and safety for 30 days postoperatively.RESULTS:No statistically significant between-treatment difference was detected in successful clinical response rates at the end of the study (72% for each group). The incidence of primary wound infections at the time of hospital discharge was also similar: 21% in patients treated with alatrofloxacin and 18% in those treated with cefotetan. Safety, established by the incidence of adverse events, did not differ statistically between the groups.CONCLUSIONS:A single intravenous dose of alatrofloxacin given within 4 hours prior to surgery was as effective as an intravenous dose of cefotetan in the prevention of postoperative infectious complications in patients undergoing elective colorectal surgery. The safety profiles of the two medications were similar.

BACKGROUND:In 1990, when the Program on the Surgical Control of the Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the conclusion that effective lipid modification reduces progression of atherosclerosis, the differences for the end points of overall mortality and mortality from atherosclerotic coronary heart disease (ACHD) did not reach statistical significance.METHODS:The Program on the Surgical Control of the Hyperlipidemias recruited men and women with a single documented myocardial infarction between the ages of 30 and 64 years who had a plasma cholesterol level higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140 mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet control group and 421 to the diet plus partial ileal bypass intervention group. Mean patient follow-up for this 5-year posttrial report was 14.7 years (range, 12.2-20 years).RESULTS:At 5 years after the trial, statistical significance was obtained for differences in overall mortality (P = .049) and mortality from ACHD (P = .03). Other POSCH end points included overall mortality (left ventricular ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and unstable angina (P<.001), incidence of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical peripheral vascular disease (P = .02). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer. All POSCH patients have been available for follow-up.CONCLUSION:At 5 years after the trial, all POSCH mortality and atherosclerosis end points, including overall mortality and mortality from ACHD, demonstrated statistically significant differences between the study groups.

BACKGROUND:Trovafloxacin, a new broad-spectrum fourth-generation quinolone, has in vitro activity against most gram-negative and gram-positive anaerobes and aerobes. Trovafloxacin is available as both an intravenous formulation, alatrofloxacin, and a single daily oral tablet. Excellent tissue pharmacokinetics and oral bioavailability suggest usefulness in the treatment of complicated intra-abdominal infections. Thus, the efficacy of alatrofloxacin followed by oral trovafloxacin was compared with the standard regimen of intravenous imipenem/cilastatin followed by oral amoxicillin/clavulanic acid in this prospective, multicenter, double-blind trial.METHODS:Patients were randomized to receive either 300 mg alatrofloxacin daily followed by 200 mg oral trovafloxacin daily or 1 g imipenem/cilastatin intravenously thrice daily followed by 500 mg oral amoxicillin/clavulanic acid thrice daily for up to 14 days following surgical intervention of a documented intra-abdominal infection. Efficacy was assessed at the end of therapy and at follow-up (day 30).RESULTS:At the end of the study, cure or improvement occurred in 83% (129/156) and 84% (127/152) of clinically evaluable patients in the trovafloxacin and comparative groups, respectively. Pathogen eradication rates, adverse-event profiles, and significant laboratory abnormalities were comparable between groups.CONCLUSION:Intravenous alatrofloxacin with or without oral trovafloxacin was as effective as intravenous imipenem/cilastatin followed by oral amoxicillin/clavulanic acid in complicated intra-abdominal infections.

Early diagnosis and timely treatment of extremity vascular injuries are essential if limb salvage and limb function are to be optimized. Careful and repeated clinical examination and ankle/brachial doppler indices are pivotal for early diagnosis. Routine arteriography for proximity injury is neither cost effective nor clinically indicated and minimal non-occlusive arterial injuries do not require vascular repair. An algorithm for the diagnostic evaluation and treatment of patients with penetrating extremity trauma is presented. The early diagnosis of compartment syndrome is stressed.

Surgical repair of an abdominal aortic aneurysm in conjunction with radical cystectomy and orthotopic urinary diversion can be safely performed without morbidity secondary to excessive blood loss, operative time, or vascular graft infection. The techniques required for this combined procedure and a case report are discussed.

Successful management of the difficult peripheral vascular injury requires a multidisciplinary approach. Prompt recognition of the vascular injury and adherence to the recognized principles of vascular repair provide a successful short-term surgical result. The long-term consequences of an injury are determined by the associated orthopedic, soft tissue, and nerve injuries.

The benefit of preoperative cardiac evaluation in the diabetic patient undergoing peripheral vascular surgery is uncertain. To investigate this issue we performed a retrospective review of 192 procedures performed in diabetic patients for chronic lower extremity arterial occlusive disease. The incidence of adverse postoperative cardiac events was determined, as well as its association with several preoperative factors including symptoms of coronary artery disease (CAD), extent and results of preoperative noninvasive cardiac evaluation, and operative site (aorta vs. lower extremity). The overall death and cardiac complication rates were 10.2% for lower extremity and 25.7% for aortic procedures (p = 0.02). For myocardial infarction and cardiac death alone, the rates were 5.1% and 5.7%, respectively (p > 0.10). Although a history of symptomatic CAD predicted the occurrence of any cardiac complication (28.3% vs. 8.2% [p < 0.01] for the aortic and lower extremity revascularization groups combined), no factor was found to be associated with the occurrence of myocardial infarction and cardiac death alone. In patients with a history of symptomatic CAD, there was no significant difference in the incidence of complications whether or not preoperative noninvasive cardiac testing was performed (28.1% vs. 28.6%, p > 0.10) or, if testing was performed, if the results were abnormal or normal (35.3% vs. 20.0%, p > 0.10). Similar results were obtained in patients with no history of symptomatic CAD. In summary, this retrospective review of our experience with noninvasive evaluation to detect CAD in diabetic patients undergoing peripheral vascular surgery failed to show any benefit in terms of reducing the incidence of postoperative cardiac events.

We compared the findings of intraoperative color duplex scanning and completion arteriography in patients undergoing infrainguinal vein bypasses to identify hemodynamic abnormalities that could result in a predisposition to early or late graft failure. We reviewed the records of 72 patients who underwent 81 vein bypass graft procedures. Three intraoperative diagnostic methods were used. In 28 procedures (group I) both color duplex and completion arteriography were used, in 21 procedures (group II) only color duplex was used, and in 26 procedures (group III) only completion arteriography was used. Grafts were followed using a duplex surveillance protocol for a mean interval of 16.1 months. Nine grafts in group I showed an abnormality on the duplex scan but not on the completion arteriogram. Seven grafts had a peak systolic velocity (PSV) greater than 200 cm/sec and two had a PSV less than 45 cm/sec. These findings led to six immediate repairs, one early revision, and two late revisions. Arteriography demonstrated additional defects in two procedures but repairs were not performed. In group II duplex scans showed an abnormality in eight procedures (seven grafts with PSV 200 to 250 cm/sec and one graft with a retained valve) resulting in three immediate repairs and five late revisions. In the remaining 13 procedures in group II, duplex scans were normal and no revisions were required during follow-up. In group III defects were detected by arteriography in four procedures (> 50% stenosis in three grafts and one arterial spasm) leading to three immediate repairs. In the remaining 22 studies arteriograms were interpreted as normal; however, seven of these grafts required late revisions. Our data suggest that grafts that appear normal on intraoperative duplex scans are not likely to develop a stenosis requiring revision. Intraoperative duplex ultrasound may be superior to completion arteriography.